CRYM p.Gln158=
c.474G>A · rs371633413 · VCV498287
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0353%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.59 | GERP -2.2, phastCons 1 |
| Overall | ||
| CADD | 6.74 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0353%
European (non-Finnish) · 184/521,062 alleles
Filtering AF
0.0311%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0295%
Overall
0.0236%
191/810,088 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0353% | 2,832 |
| Remaining individualsnot grpmax-eligible | 0.0103% | 9,736 |
| African / African-American | 0.00585% | 17,097 |
| Finnishnot grpmax-eligible | 0.00247% | 40,540 |
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- CRYM
- Protein
- p.Gln158=
- Coding
- c.474G>A
- MANE Select
- NM_001376256
- dbSNP
- rs371633413
- Type
- single nucleotide variant
- Location
- chr16:21269805 (GRCh38)
- Gene constraint
- LOEUF 0.841 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 96.06 · 1 PDB
- Residue 158
- an α-helix
Similar variants
- CRYM p.Ala178Glu Uncertain significance ★★ ⚠ same type
- CRYM p.Glu172Gly Uncertain significance ★★ ⚠ same type
- CRYM p.Leu72Val Uncertain significance ★★ ⚠ same type
- CRYM p.Met295Ile Uncertain significance ★★ ⚠ same type
- CRYM p.Thr95Ser Uncertain significance ★★ ⚠ same type
- CRYM p.Val4Leu Uncertain significance ★★ ⚠ same type
- CRYM c.171-118C>T Benign ★★ same type
- CRYM c.171-19G>A Likely benign ★★ same type
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/crym-p-gln158 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown